NERVIANO, Italy, October 23 /PRNewswire/ --
- First Responses in Solid Tumours Reported.
Aurora inhibitors play a key role in cell duplication and are implicated in both the onset and progression of numerous types of tumour. A lecture focusing on Aurora kinase inhibitors will be presented today by Dr. Bernard Laffranchi during the 20th EORTC-NCI-AACR Symposium "Molecular Targets and Cancer Therapeutics" organised from 21st to 24th October 2008 in Geneva. Dr Laffranchi, Director Clinical Research of Nerviano Medical Sciences, the largest R&D cancer drug stand alone company in Europe (http://www.nervianoms.com) has been invited to give a presentation on the state-of-the-art of Aurora kinase inhibitors, providing a comprehensive summary of ongoing clinical studies being performed on this molecular target to which increasing attention is being paid by the experts.
"Nerviano Medical Sciences (NMS) has been chosen by these prestigious scientific societies in view of the fact that the Italian centre has a recognized leadership in research & development of Aurora inhibitors," explains Francesco Colotta, Research & Development Director at NMS. Indeed, compounds capable of inhibiting activity of this kinase family and displaying anti-tumour efficacy in a wide range of solid and blood cancers models were first identified at Nerviano. Moreover, emphasises Dr. Colotta, the Aurora inhibitors discovered at Nerviano were the first to be evaluated in patients and to undergo clinical development.
"This symposium will be organised in a particularly pragmatic fashion and provides a wide-ranging overview of all data collected with regard to future treatment of patients," underlines Dr. Colotta. "Preliminary results of human clinical Phase II trials with Aurora inhibitors carried out by NMS are underway," continues Dr. Colotta. The product at the most advanced stage of development is PHA 739358, a selective inhibitor of the entire Aurora kinase family (A, B and C), which, terminated Phase I studies and is now undergoing clinical Phase II trials in solid tumours and blood cancers at some of the most widely acknowledged international clinics: Erasmus Medical Center, Rotterdam, Policlinico Gemelli, Rome, Gustave Roussy, Villejuif, France, University of California, Los Angeles (UCLA) and University of California, San Francisco (UCSF) Fox Chase Cancer Center, Philadelphia, to name some of the most important. "This low molecular weight compound is inhibiting growth of tumour cells by interacting with mitosis during cell proliferation for which Aurora kinases are essential."
During the EORTC-NCI-AACR Symposium a recently identified biomarker used to assess PHA 739358 activity will also be presented by Dr. Bernard Laffranchi, NMS. The marker, Histone H3, is phosphorylated by Aurora kinases and is strongly reduced following treatment with the compound. "This phenomenon was initially highlighted in experimental tumour models and was recently confirmed by findings obtained from patient biopsies", explains Laffranchi. A decreased phosphorylation of Histone H3 in patients treated with PHA 739358 supports this hypothesis whereby the anti-cancer activity exerted by the compound is mediated through inhibition of Aurora kinases.
"Results obtained to date in humans reveal that PHA 739358 is a molecule with a good tolerability profile and promising hints of activity were seen," states Dr. Colotta. In Phase I trials, PHA 739358 was administered intravenously to patients with advanced and progressive solid tumours. In 20% of patients treated the disease stabilised, half of which for a period exceeding six months in subjects affected by cancer of the kidney, oesophagus, ovary, colon or non-small cell lung cancer (NSCLC). Toxicity, ranged from slight to moderate, was reversible and easily manageable from a clinical point of view. "In Phase I trials a partial response to treatment with this molecule was also observed in a patient with small cell lung cancer (SCLC) who, upon treatment, displayed a 77% reduction of one cancer lesion and resolution of a second one," concludes Dr. Colotta.
Abstract no: 243, presented 10.15 hrs on Thursday 23 October, Plenary
Nerviano Medical Sciences
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|SOURCE Nerviano Medical Sciences|
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